title: Physiopathology of somatolactotroph cells: from transduction mechanisms to cotargeting therapy.
abstract: In pituitary somatolactotroph cells, G protein-coupled receptors and receptor tyrosine kinases binding their specific ligands trigger an enzymatic cascade that converges to MAP kinase activation in the subcellular compartment. Different signaling pathways, such as AC/cAMP/PKA and PI3K/Akt pathways, interact with MAP kinase to regulate key physiological functions, such as hormonal secretion and cell proliferation. Abnormalities affecting these signaling pathways have been identified as preponderant factors of pituitary tumorigenesis. In addition to trans-sphenoidal surgery, somatostatin analogs are used to control hormonal hypersecretion in GH-secreting adenomas. However, a subset of these tumors remains uncontrolled with these treatFments, calling for new therapeutic approaches. In these cases, novel multivalent somatostatin analogs or new somatostatin-dopamine chimeric molecules could be of interest. Another attractive therapeutic approach may be to use one or several inhibitors acting downstream in the signaling pathway, such as mammalian target of rapamycin inhibitor. Cotargeting therapy and gene therapy are promising tools for these problematic pituitary tumors.
authors.affiliation: Research Center of Neurobiology and Neurophysiology of Marseille, CRN2M, UMR 6231 CNRS, University of Mediterranée, Institut Fédératif Jean Roche, Marseille, France. thomascuny@hotmail.com
authors.forename: Thomas
authors.initials: T
authors.lastname: Cuny
authors.forename: Corinne
authors.initials: C
authors.lastname: Gerard
authors.forename: Alexandru
authors.initials: A
authors.lastname: Saveanu
authors.forename: Anne
authors.initials: A
authors.lastname: Barlier
authors.forename: Alain
authors.initials: A
authors.lastname: Enjalbert
mesh_terms: D000818:Animals; D006801:Humans; D010902:Pituitary Gland / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction